The main objective of the proposed work is to develop appropriate and practicable animal models of mental deficiency and other functional deficits associated with congenital defects of the brain in man. The purpose of developing these models is to make possible more effective screening of substances that may produce similar defects in man, as well as to permit analysis of anatomic, pathologic, physiological, and biochemical changes associated with (and presumably causative of) mental deficiency. Specific aims of this project are to determine the functional, neuroanatomical, and neurochemical changes associated with several different brain malformations produced in the ferret by treatment with methyazoxymethanol acetate on different days of gestation. During the coming year, emphasis will be placed studying lissencephalic ferrets and ferrets with cerebellar hypoplasia. The functional studies will include tests of sensory motor development, maze learning, anticipatory behavior, and changes in resting EEG. The neuroanatomical and neuropathological work will focus on the development and characterization of lissencephaly. The neurochemical studies will deal with lipids. BIBLIOGRAPHIC REFERENCES: Haddad, R. K., Rabe, A., Dumas, A., & Lazar, J. W. Position reversal deficit in young ferrets. Developmental Psychobiology, 1976, 9, #4 (July), in press. Haddad, R., & Rabe, A. Analysis of species differences in functional consequences of chemically induced cerebellar dysplasia. Teratology, 1976, 12. (Abstract), in press.